Journal
NATURE BIOMEDICAL ENGINEERING
Volume 2, Issue 11, Pages 841-849Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41551-018-0263-5
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Funding
- National Institutes of Health [R01 AR062920, F30 AR069472, S10 OD016264]
- Children's Healthcare of Atlanta
- Georgia Institute of Technology
- Cystic Fibrosis Foundation [MCCART15R0]
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Lung infections associated with pneumonia, or cystic fibrosis caused by Pseudomonas aeruginosa or other bacteria, result in significant morbidity and mortality, in part owing to the development of multidrug resistance, also against last-resort antibiotics. Lytic bacteriophages (that is, viruses that specifically kill bacteria) can reduce lung-associated infections, yet their clinical use is hindered by difficulties in delivering active phages to the deep lung. Here, we show that phage-loaded polymeric microparticles deposit throughout the lung via dry powder inhalation and that they deliver active phages. Phage-loaded microparticles effectively reduced P. aeruginosa infections and the associated inflammation in wild-type and cystic fibrosis trans-membrane-conductance-regulator knockout mice, and rescued the mice from pneumonia-associated death. These polymeric microparticles might constitute a clinically translatable therapy for eradicating hospital-acquired lung infections and infections associated with cystic fibrosis.
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